Abstract:
:Although branchpoint recognition is an essential component of intron excision during the RNA splicing process, the branchpoint itself is frequently assumed to be a basal, rather than regulatory, sequence feature. However, this assumption has not been systematically tested due to the technical difficulty of identifying branchpoints and quantifying their usage. Here, we analyzed ∼1.31 trillion reads from 17,164 RNA sequencing data sets to demonstrate that almost all human introns contain multiple branchpoints. This complexity holds even for constitutive introns, 95% of which contain multiple branchpoints, with an estimated five to six branchpoints per intron. Introns upstream of the highly regulated ultraconserved poison exons of SR genes contain twice as many branchpoints as the genomic average. Approximately three-quarters of constitutive introns exhibit tissue-specific branchpoint usage. In an extreme example, we observed a complete switch in branchpoint usage in the well-studied first intron of HBB (β-globin) in normal bone marrow versus metastatic prostate cancer samples. Our results indicate that the recognition of most introns is unexpectedly complex and tissue-specific and suggest that alternative splicing catalysis typifies the majority of introns even in the absence of differences in the mature mRNA.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Pineda JMB,Bradley RKdoi
10.1101/gad.312058.118subject
Has Abstractpub_date
2018-04-01 00:00:00pages
577-591issue
7-8eissn
0890-9369issn
1549-5477pii
gad.312058.118journal_volume
32pub_type
杂志文章abstract::Outward migration of epidermal progenitors occurs with induction of hundreds of differentiation genes, but the identities of all regulators required for this process are unknown. We used laser capture microdissection followed by RNA sequencing to identify calmodulin-like 5 (CALML5) as the most enriched gene in differe...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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doi:10.1101/gad.13.18.2439
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2005-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
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更新日期:2013-12-15 00:00:00
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journal_title:Genes & development
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doi:10.1101/gad.7.7b.1364
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.8.925
更新日期:1995-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1700
更新日期:1988-12-01 00:00:00
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journal_title:Genes & development
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doi:10.1101/gad.1584307
更新日期:2007-11-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.24.3209
更新日期:1999-12-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.20.2588
更新日期:1996-10-15 00:00:00
abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::Transcription of frog rDNA by mouse cell factors is the only documented exception to the observed species selectivity of rRNA gene expression. This heterologous transcription is authentic in that it uses the normal frog upstream and core promoter domains, as well as the normal mouse polymerase I transcription factors,...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.1.52
更新日期:1990-01-01 00:00:00
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更新日期:1998-02-01 00:00:00
abstract::Hepatocyte nuclear factor 1 (HNF-1) is a transcriptional regulatory protein possibly involved in the activation of many liver-specifically expressed genes. HNF-1 mRNA is restricted to a small number of tissues, suggesting that the HNF-1 gene itself is regulated at the transcriptional level. We have isolated and charac...
journal_title:Genes & development
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doi:10.1101/gad.5.12a.2225
更新日期:1991-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.6.1072
更新日期:1993-06-01 00:00:00
abstract::The amyloid precursor protein (APP) has garnered considerable attention due to its genetic links to Alzheimer's disease. Death receptor 6 (DR6) was recently shown to bind APP via the protein extracellular regions, stimulate axonal pruning, and inhibit synapse formation. Here, we report the crystal structure of the DR6...
journal_title:Genes & development
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doi:10.1101/gad.257675.114
更新日期:2015-04-15 00:00:00
abstract::Spliceosome assembly has been characterized as the ordered association of the snRNP particles U1, U2, and U4/U6.U5 onto pre-mRNA. We have used an in vitro trans-splicing/cross-linking system in Saccharomyces cerevisiae nuclear extracts to examine the first step of this process, 5' splice site recognition. This trans-s...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2001-08-01 00:00:00
abstract::During gastrulation of Xenopus embryos the prospective mesoderm is induced initially with domains of dorsal and ventral fate, then further patterned to generate somitic mesoderm by signals from the gastrula organizer. Although Xwnt-8 is expressed in future ventrolateral mesoderm and induces prospective epidermis to di...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.21.2805
更新日期:1996-11-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.4.481
更新日期:1994-02-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2008-02-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2016-04-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章,评审
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更新日期:2018-09-01 00:00:00
abstract::TFIID is a multisubunit protein containing the TATA box-binding polypeptide (TBP) and associated factors (TFIID-TAFs) required for activated transcription by RNA polymerase II. TBPs from different eukaryotes contain a highly conserved carboxy-terminal domain and very divergent amino-terminal domains. Earlier studies p...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1993-02-01 00:00:00